In patients with chronic infection with hepatitis C virus (HCV) genotype 1, treatment with peginterferon alfa and ribavirin for 48 weeks results in rates of sustained virologic response of 40 to 50%. Telaprevir is a specific inhibitor of the HCV serine protease and could be of value in HCV treatment.
Methods A total of 334 patients who had chronic infection with HCV genotype 1 and had not been treated previously were randomly assigned to receive one of four treatments involving various combinations of telaprevir (1250 mg on day 1, then 750 mg every 8 hours), peginterferon alfa-2a (180 µg weekly), and ribavirin (dose according to body weight). The T12PR24 group (81 patients) received telaprevir, peginterferon alfa-2a, and ribavirin for 12 weeks, followed by peginterferon alfa-2a and ribavirin for 12 more weeks. The T12PR12 group (82 patients) received telaprevir, peginterferon alfa-2a, and ribavirin for 12 weeks. The T12P12 group (78 patients) received telaprevir and peginterferon alfa-2a without ribavirin for 12 weeks. The PR48 (control) group (82 patients) received peginterferon alfa-2a and ribavirin for 48 weeks. The primary end point, a sustained virologic response (an undetectable HCV RNA level 24 weeks after the end of therapy), was compared between the control group and the combined T12P12 and T12PR12 groups.
Results The rate of sustained virologic response for the T12PR12 and T12P12 groups combined was 48% (77 of 160 patients), as compared with 46% (38 of 82) in the PR48 (control) group (P=0.89). The rate was 60% (49 of 82 patients) in the T12PR12 group (P=0.12 for the comparison with the PR48 group), as compared with 36% (28 of 78 patients) in the T12P12 group (P=0.003; P=0.20 for the comparison with the PR48 group). The rate was significantly higher in the T12PR24 group (69% [56 of 81 patients]) than in the PR48 group (P=0.004). The adverse events with increased frequency in the telaprevir-based groups were pruritus, rash, and anemia.
Conclusions In this phase 2 study of patients infected with HCV genotype 1 who had not been treated previously, one of the three telaprevir groups had a significantly higher rate of sustained virologic response than that with standard therapy. Response rates were lowest with the regimen that did not include ribavirin. (ClinicalTrials.gov number, NCT00372385 [ClinicalTrials.gov].
Source Information
From Assistance Publique–Hôpitaux de Paris, Henri Mondor Hospital, University of Paris 12 and INSERM Unité 955, Créteil (C.H., J.-M.P.); Université Paris Descartes, INSERM Unité 567, and Assistance Publique–Hôpitaux de Paris, Cochin Hospital Paris, Paris (S.P.); INSERM Unité 724, University Hospital of Nancy, Vandoeuvre-les-Nancy (J.-P.B.); and St. Joseph Hospital, Marseille (M.B.) — all in France; J.W. Goethe University Hospital, Frankfurt (N.F., S.Z.); and University Hospital of Cologne, Cologne (T.G.) — both in Germany; Royal Free Hospital, London (G.D.); Medical University of Vienna, Vienna (P.F.); and Vertex Pharmaceuticals, Cambridge, MA (S. Gharakhanian, L.B., L.M., S. George, T.K., A.K., R.S.K., J.A.).
Drs. Hézode and Forestier contributed equally to this article.
Address reprint requests to Dr. Pawlotsky at the Department of Virology, Hôpital Henri Mondor, 51 Ave. du Maréchal de Lattre de Tassigny, 94010 Créteil, France
Christophe Hézode, M.D., Nicole Forestier, M.D., Geoffrey Dusheiko, M.D., Peter Ferenci, M.D., Stanislas Pol, M.D., Tobias Goeser, M.D., Jean-Pierre Bronowicki, M.D., Marc Bourlière, M.D., Shahin Gharakhanian, M.D., Leif Bengtsson, B.S.C., Lindsay McNair, M.D., M.P.H., Shelley George, M.D., Tara Kieffer, Ph.D., Ann Kwong, Ph.D., Robert S. Kauffman, M.D., Ph.D., John Alam, M.D., Jean-Michel Pawlotsky, M.D., Ph.D., Stefan Zeuzem, M.D., for the PROVE2 Study Team
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